ClinVar Miner

Submissions for variant NM_024537.4(CARS2):c.563C>T (p.Thr188Met)

gnomAD frequency: 0.00030  dbSNP: rs142034206
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000557366 SCV000655874 uncertain significance Combined oxidative phosphorylation defect type 27 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 188 of the CARS2 protein (p.Thr188Met). This variant is present in population databases (rs142034206, gnomAD 0.05%). This missense change has been observed in individual(s) with epilepsy and intellectual disability (PMID: 30139652). ClinVar contains an entry for this variant (Variation ID: 475631). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001266184 SCV001444356 uncertain significance Inborn genetic diseases 2018-11-19 criteria provided, single submitter clinical testing
Baylor Genetics RCV000557366 SCV001524880 uncertain significance Combined oxidative phosphorylation defect type 27 2020-03-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Fulgent Genetics, Fulgent Genetics RCV000557366 SCV002791794 uncertain significance Combined oxidative phosphorylation defect type 27 2021-09-16 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000557366 SCV003830590 uncertain significance Combined oxidative phosphorylation defect type 27 2019-11-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003403337 SCV004122420 uncertain significance not specified 2023-10-30 criteria provided, single submitter clinical testing Variant summary: CARS2 c.563C>T (p.Thr188Met) results in a non-conservative amino acid change located in the tRNA synthetases class I, catalytic domain (IPR032678) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00029 in 241100 control chromosomes (gnomAD). c.563C>T has been reported in the literature in individuals affected with Alpers-Huttenlocher syndrome (Samanta_2018, Almubarak_2022). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 36360262, 34690748, 34426522, 30139652). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Mayo Clinic Laboratories, Mayo Clinic RCV004791568 SCV005409652 uncertain significance not provided 2024-01-16 criteria provided, single submitter clinical testing
OMIM RCV000557366 SCV002106391 pathogenic Combined oxidative phosphorylation defect type 27 2022-03-17 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.